Oxalate binding, lactoferrin

Confirmation has come through crystallographic studies of oxalate binding to lactoferrin. The crystal structure of a hybrid complex of copper-lactoferrin, at 2.2-A resolution, has carbonate in the N-termi-nal site and oxalate in the C-terminal site (192). The oxalate ion is bound to the metal ion (Cu2+ in this case) in 1,2-bidentate mode, as anticipated (190,191), i.e., through both carboxylates (Fig. 26a). One... 

Distinct differences are also seen when anions other than C032 are used. The crystal structure of oxalate-substituted diferric lactoferrin shows differences in the anion binding in the two sites in the C-site the oxalate is symmetric bidentate, whereas in the N-site it is asymmetric (193). When Cu2+ is the metal ion the oxalate binding differences become even more pronounced. Copper-transferrin binds oxalate only in its N-terminal site (91). Copper-lactoferrin and copper-ovotransfer-rin each bind two oxalate ions but binding occurs preferentially in the C-lobe (157,192). These different affinities mean that hybrid complexes can be prepared with oxalate in one site and carbonate in the other (92, 157, 192). The use of oxalate as synergistic anion gives rise to spectroscopically distinct sites for other metal ions also (171). 

Fig. 26. Binding modes for anions other than carbonate. In (a) the mode of binding of oxalate to human lactoferrin, as determined crystallographically (192,193), is shown. In b is a generalized model for synergistic anion binding to transferrins, based on EPR studies (191) and the crystallographic results for oxalate. From Shongwe et al. (192), with permission.

Baker HM, Anderson BF, Brodie AM, Shongwe MS, Smith CA, Baker EN. 1996. Anion binding by transferrins importance of second-shell effects revealed by the crystal structure of oxalate-substituted diferric lactoferrin. Biochemistry 35(28) 9007-9013. 

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